This application is to establish the UNC-Malawi Cancer Consortium (UNC-MCC), to develop capacity and conduct high-impact research focused on HIV-associated cancers. The consortium builds on longstanding collaborations between the University of North Carolina at Chapel Hill (UNC-CH), Lighthouse Trust, Malawi Ministry of Health, and University of Malawi College of Medicine. These partnerships have resulted in internationally recognized contributions for HIV care and prevention in sub-Saharan Africa. This infrastructure can now be leveraged for HIV-associated malignancies. UNC-MCC is focused on the herpesvirus-associated cancers, Kaposi sarcoma (KS), and lymphoma. Our consortium will be led by three principal investigators with highly complementary expertise (Satish Gopal MD, clinical research; Sam Phiri PhD, implementation science; Blossom Damania PhD, virology). The second of three research projects undertaken by UNC-MCC attempts to elucidate subsets of HIV-associated KS in Malawi to improve outcomes. The project is led by three co-PIs, Dr. Agnes Moses (UNC Project-Malawi), Joe Gumulira (Lighthouse Trust), and Dr. Dirk Dittmer (Lineberger Comprehensive Cancer Center). The project addresses a central problem that despite significant heterogeneity across a large KS population in Malawi, it is difficult to prospectively identify patients who are likely have relapsed or refractory disease. This is a population for whom better treatments are urgently needed. We will attempt to better understand KS heterogeneity through the following aims: (1) to develop a prognostic score using comprehensive clinical, laboratory, and biomarker data for recurrent or progressive disease; (2) to establish prevalence of KSHV-associated lymphoproliferative diseases in the KS population and effects on outcomes; (3) to identify KS-associated herpesvirus genomic features in tumor specimens which are associated with recurrent or progressive disease; and (4) to compare patient and tumor characteristics between KS that develops on and off ART. Recently completed work by our group (the AIDS Malignancy Consortium S001 study) has already demonstrated novel and important insights into KS biology in Malawi. This proposal seeks to build on these successes and collaborations to improve KS care.